1. Technical Field of the Invention
The present invention relates to new uses of compounds, particularly a diterpenoid Galanal B, in the regulation of blood glucose levels.
2. Background
Glucagon-like peptide-1 (GLP-1) analogues are a new class of hypoglycemic agents. GLP-1 is a member of the incretin family, which comprises gastrointestinal hormones that help control blood glucose levels after meals. GLP-1 exerts its functions by specific binding to GLP-1 receptor. GLP-1 receptor (GLP-1R) is widely distributed. In addition to pancreatic tissue, GLP-1 receptor is also distributed in the brain, lung, heart, kidney, etc. The wide distribution of this receptor contributes to the wide range of its functions.
GLP-1 bind specifically to the GLP-1 receptor on the pancreatic beta cells. Activation of GLP-1R leads to stimulation of the adenylyl cyclase pathway, which eventually leads to increased insulin synthesis and release. In addition to the increased insulin synthesis and release, GLP-1 binding to its receptor also inhibits the production of glucagon and maintains constant levels of blood glucose after meals. Furthermore, GLP-1 also has a neuron regulatory function, which can delay gastric emptying and reduce appetite. At the same time, the hypoglycemic effect of GLP-1 is self-limiting and will not result in hypoglycemia (i.e., will not result in over reduction in blood glucose levels). These properties are beneficial for diabetes controls. Therefore, drugs having GLP-1-like activities are ideal for diabetes controls and treatments. Accordingly, search for GLP-1 analogs has become a research focus for new drug developments.
However, GLP-1 is a peptide and is rapidly degraded by DPP-IV (dipeptidyl peptidase IV) in vivo, leading to loss of its biological activities. The in vivo half-life of GLP-1 is less than 2 min, necessitating continuous intravenous infusion or continuous subcutaneous injection to maintain its effects. This property greatly limits the clinical applications of GLP-1. Therefore, in recent years, there have been great efforts focusing on the research and development of long-lasting GLP-1 analogs and DPP-N inhibitors.
Currently available GLP-1 analogs, including Byetta® (Exenatide; Amylin Pharmaceuticals, San Diego, Calif.) and Victoza® (liraglutide; Novo Nordisk, Denmark), can effectively control blood glucose levels, without causing hypoglycemia, in type II diabetes patients who did not respond to other oral blood glucose lowering medications. The studies found that these GLP-1 analogues can reduce patients' body weights and control blood glucose at more stable levels. In addition, these GLP-1 analogs can maintain, and may even improve, the basal metabolisms and post glucose-stimulation beta cell functions in type II diabetic patients, and delay disease progression.
To date, research on GLP-1 analogs is mainly focused on peptide analogs or regulators. Because peptide drugs cannot be given by oral administration and they can be easily degraded, it would be desirable to have other types of drugs that have activities similar to GLP-1 analogs.